Archive for the ‘Genetic Testing’ Category
Predictive genetic testing helps breast cancer patient Tammy Goodsell – East Kent Hospitals University NHS Foundation Trust
Predictive genetic testing helps breast cancer patient Tammy Goodsell East Kent Hospitals University NHS Foundation Trust
View original post here:
Predictive genetic testing helps breast cancer patient Tammy Goodsell - East Kent Hospitals University NHS Foundation Trust
Genetic Testing – Mayo Clinic Health System
Know your numbers: Family health history
Genes play a role in your health. Understanding your family's heart and health history is key to understanding your risk of heart disease. Find out which relatives you should talk to about family health history.
See the article here:
Genetic Testing - Mayo Clinic Health System
However good genetic testing gets, there will always be plenty of space for you to make a total mess of things entirely of … – CyclingWeekly
However good genetic testing gets, there will always be plenty of space for you to make a total mess of things entirely of ... CyclingWeekly
Read the original:
However good genetic testing gets, there will always be plenty of space for you to make a total mess of things entirely of ... - CyclingWeekly
Genetic Testing: What You Should Know – Healthline
People often turn to genetic testing to investigate possible health conditions that run in families or even explore their own family history and heritage.
With advancements in technology, genetic testing is becoming more precise and more affordable than before. This opens it up to a wider range of people seeking answers to questions about their health and family.
This article will describe the clinical and research purposes of genetic testing, the health conditions it may help detect, and what you may want to consider when talking with your healthcare team about this type of testing.
Genetic testing is a broad term used to describe a medical test that identifies changes in a DNA sequence or chromosomal structure.
Genetic testing can also measure results of gene changes, like an RNA analysis of a genes expression. It may analyze and measure the specific makeup of a certain gene, in order to help better identify the particular genetic makeup that might be shared with others or signal a possible health concern.
There are many uses for genetic testing. It can help people plan for the future by telling them the likelihood of developing a specific health condition.
It can also be used to help diagnose rare genetic conditions or to get information for better precision medicine when tailoring treatment options for an individual.
People may opt to have genetic testing done during pregnancy to rule out specific hereditary conditions, such as Down syndrome or potential problems with the unborn childs number of sex chromosomes.
According to the National Institutes of Health, genetic tests are available for many different genetic conditions.
Genetic testing can also be used to broadly trace ones ancestry and ethnicity or to provide information about biological parents and close relatives.
Clinical genetic testing aims to find out about any likelihood of an inherited genetic condition in a particular person and/or their family. These results are added to the medical record, and they can help inform people about the best course of treatment or prevention.
Research genetic testing, on the other hand, occurs when genetic testing is done on a person who volunteers for a clinical trial. The testing is done as part of a research study.
The outcomes of research-based genetic testing arent available to the participants or their doctors. The outcomes are also not added to anyones medical record, because theyre simply to help inform the research study.
People wont personally benefit from this type of genetic testing, and it cant be used to make individual diagnoses. But it does contribute to research.
Genetic testing isnt required during pregnancy. But many people opt for it to rule out any life threatening conditions to the fetus or other chromosomal conditions, such as Down syndrome, trisomy 18 (Edwards syndrome), or trisomy 13 (Patau syndrome).
There are certain factors that may increase someones likelihood to opt for genetic testing, including:
Advanced maternal age increases the likelihood that the fetus may have chromosomal irregularities, and having genetic testing on the fetus can rule those out.
Genetic testing is available for the following types of cancer:
Getting genetic testing for cancer can help you predict your risk of developing a certain type of cancer, but it doesnt predict that you will or wont develop any type of cancer.
It may, however, find out if you have genes that may pass an increased cancer risk onto your children (the BRCA gene for breast cancer, for example).
About 13% of women will develop breast cancer at some point in their lives, according to the American Cancer Society (ACS). By contrast, up to 72% who inherit the BRCA1 variant and as many as 69% of people who inherit the BRCA2 variant will develop breast cancer during their lifetime, according to a 2017 study.
Even someone who has a high likelihood of developing breast cancer if they have the BRCA1 or BRCA2 variant may never develop the disease. Also, someone who doesnt have these gene mutations may go on to develop breast cancer in their lifetime.
Having access to that information may help you make informed decisions about healthcare procedures and genetic testing to detect possible cancers.
Genetic testing cant detect or help diagnose all conditions, such as autism. However, genetic testing can be used to help predict or assess ones risk for many health issues, including conditions that newborns should be screened for. These conditions may include:
The following conditions can be genetically tested in utero:
While theres no genetic test for diabetes, children who have a sibling with type 1 diabetes may opt for an antibodies test that measures the antibody response to insulin, the islet cells in the pancreas, or to an enzyme called glutamic acid decarboxylase (GAD).
High levels indicate that a child has a higher likelihood of developing type 1 diabetes, but it doesnt guarantee that theyll develop type 1 diabetes.
Talk with your doctor if youre interested in getting genetic testing either for you or your children. If youre pregnant, you may want to opt for genetic testing for your baby, especially if any of the previously mentioned conditions run in your family.
Genetic testing can either be done at home with a saliva sample or in a laboratory, with a small blood sample.
In pregnant people, genetic testing is usually done via amniotic fluid through amniocentesis, or the placenta, through chorionic villus sampling (CVS).
Testing can also be done directly on the embryo during in vitro fertilization (IVF). Results can take a few weeks after samples are drawn.
You should consider genetic testing if theres a particular condition that runs in the family and you might be concerned about it materializing in your life.
Additionally, you may consider genetic testing if you want to learn what the risk is for a future pregnancy or to see if youre a carrier of a genetic condition (or if your child is a carrier or has a genetic condition themselves).
It can guide treatment and prevention planning for you and your family, especially when it comes to cancer.
People who are at higher risk for having a child with a genetic condition may opt for genetic testing. This includes:
People may also opt for genetic testing for simple peace of mind if their risk tolerance is low. Talk with your doctor or a genetic counselor if you want more information or if you feel that genetic testing is appropriate for you or your children.
Genetic testing is used for both research and clinical reasons, and it can be used to help trace family lineage as well as possible health conditions, including cancer.
While genetic testing isnt required during pregnancy, some people who are pregnant may consider it to evaluate the possible risk of health conditions that can be passed on to a child.
Read the original here:
Genetic Testing: What You Should Know - Healthline
Genetic Testing: How It Works, Types, and Diagnosis | Patient
What are DNA, genes and chromosomes?
Your body is made up of millions of tiny cells. Different types of cells form the different structures of the body, including skin, muscles, nerves and also organs such as the liver and kidneys.
This image was derived from Eukaryote DNA.svg, via Wikimedia Commons
In the centre (nucleus) of most cells in your body, the DNA molecule is packaged into thread-like structures called chromosomes. You have 46 chromosomes arranged in 23 pairs. These include one pair of sex chromosomes (either XX for females and XY for males). The other chromosomes that do not determine whether we are male or female are called autosomes. There are 22 pairs of autosomes (numbered 1 to 22). One chromosome from each pair comes from your mother and one from your father.
A gene is the basic unit of your genetic material. It is made up of a sequence (or piece) of DNA and sits at a particular place on a chromosome. So, a gene is a small section of a chromosome. Each gene controls a particular feature or has a particular function in your body. For example, dictating your eye colour or hair colour, making all the various proteins in your body, etc. Each gene is part of a pair. One gene from each pair is inherited from your mother, the other from your father. Each chromosome carries hundreds of genes. Humans have between 20,000 and 25,000 genes altogether. The total of all your genes is called your genome.
DNA stands for deoxyribonucleic acid. DNA forms your genetic material. Genes, which are made up of DNA, act as instructions to make proteins. In humans, genes vary in size from just a very small amount of DNA to very large amounts of DNA.
Proteins are large, complicated molecules that play many important roles in your body. They do most of the work in cells and are required for the structure, function and regulation of your body's tissues and organs.
As our cells are multiplying all the time, our genetic information needs to stay the same. Normally, there are excellent mechanisms in place to make sure each cell gets the exact same copy of DNA, the material that makes up our genes. However, sometimes the copying mechanism makes mistakes or other problems can occur with your genetic material. Problems and abnormalities in genes can lead to genetic diseases.
Genetic testing is a type of medical test that identifies changes in chromosomes, genes or proteins. Gene tests look for abnormalities in DNA taken from a person's blood, body fluids or tissues. The tests can look for large mistakes such as a gene that has a section missing or added. Other tests look for small changes within the DNA. Other mistakes that can be found include genes that are too active, genes that are turned off, or those that are lost entirely.
Genetic tests examine a person's DNA in a variety of ways. They are all designed to identify differences between the gene being tested and what would be considered to be a normal version of the same gene.
There are different types of genetic testing which include:
These look at single genes or short lengths of DNA taken from a person's blood or other body fluids (for example, saliva) to identify large changes, such as:
An example of a genetic disorder that is tested in this way is cystic fibrosis.
However, there are limitations to genetic testing, as it is only useful if it is known that a specific genetic mutation causes a certain condition. A mutation or error in copying the DNA results in a permanent change to the DNA which can result in a number of diseases. For example, a specific gene mutation is known to cause Huntington's disease. It is therefore possible to test a blood sample for the presence or absence of this gene mutation. For many conditions - for example, diabetes - there may be any one of hundreds or even thousands of different possible mutations in a particular gene. This means genetic testing for those conditions is virtually impossible.
These look at the features of a person's chromosomes, including their structure, number and arrangement. Parts of a chromosme can be missing, be extra or even be moved to a different part on another chromosome.
There are different ways in which chromosome tests can be undertaken. These include:
Biochemical tests look at the amounts or activities of key proteins. As genes contain the DNA code for making proteins, abnormal amounts or activities of proteins can signal genes that are not working normally. These types of tests are often used for newborn baby screening. For example, biochemical screening can detect infants who have a condition affecting one of the many essential chemical reactions in the body (metabolic condition) such as phenylketonuria.
Genetic test results can confirm or rule out a suspected genetic condition or help determine a person's chance of developing or passing on a genetic disorder. More than 2,000 genetic tests are currently in use, and more are being developed all the time.
Genetic testing is performed in different ways including:
Newborn screening is done just after birth to identify genetic disorders that can be treated early in life. For example, every baby in the UK is tested for cystic fibrosis as part of the heel prick test.
Diagnostic testing is used to identify or rule out a specific genetic disorder if a baby or person has symptoms to suggest a certain genetic disorder (for example, Down's syndrome).
Carrier testing is used to identify people who carry one copy of a gene mutation (a genetic change) that, when present in two copies, causes a genetic disorder (for example, sickle cell disease). This type of test can be useful to provide information about a couple's risk of having a child with a genetic disorder.
Before birth (prenatal) testing is used to detect changes in an unborn baby's genes. This type of testing is offered during pregnancy if there is an increased risk that the baby will have a genetic or chromosomal disorder. It cannot identify all possible inherited disorders and birth defects, however.
Pre-implantation genetic testing is available for couples who are at risk of having a child with a specific genetic or chromosome disorder, eg cystic fibrosis, sickle cell disease or Huntington's disease.
Egg cells are removed from the woman's ovaries and then fertilised with sperm cells outside the body. This is called in-vitro fertilisation (or IVF). The eggs are fertilised with sperm cells to form embryos. The fertilised embryos develop for three days and then one or two cells are removed from each embryo.
The genetic material (DNA and chromosomes) from the cells are tested for the known disorder in the family history. One or two of the unaffected embryos are then transferred into the mother's womb (uterus). If the pregnancy is successful, the baby will not be affected by the disorder it was tested for.
Predictive testing is used to detect genetic mutations associated with disorders that appear after birth, often later in life. These tests can be helpful to people who have a family member with a genetic disorder but who have no features of the disorder themselves at the time of testing (for example, breast cancer associated with the BRCA1 gene). Predictive testing can identify mutations that increase a person's risk of developing disorders with a genetic basis, such as certain types of cancer.
Testing can also determine whether a person will develop a genetic disorder, such as haemochromatosis, before any signs or symptoms appear. People in families at high risk for a genetic disease have to live with uncertainty about their future and their children's future.
A genetic test result showing a known gene mutation responsible for a certain disease as not being present in a person can provide a sense of relief. However a positive result may have a devastating effect on a person's life, especially if there is no known treatment.
However for some disorders a positive result may help you to consider options to prevent the disorder. For example, women with BRAC1 are at increased risk of breast cancer and may decide to have surgery to remove their breasts (mastectomy) or to take a medicine called tamoxifen to reduce the risk. See the separate leaflet on Breast Cancer for more information.
Therefore before having predictive testing it is essential for a specialist to carefully discuss with you your risks of being affected by the disorder, how the disorder would affect you and the benefits and risks of having a genetic test for the disorder. See the section on genetic counselling below.
Forensic testing uses DNA sequences to identify a person for legal purposes. Unlike the tests described above, forensic testing is not used to detect gene mutations associated with disease. This type of testing can also be used to work out the paternity of a child. Forensic testing can also be used for identifying human remains when identification is not possible by other means - for example, after a natural disaster such as a fire or tsunami.
Genetic testing usually involves taking a sample of blood or tissue. In adults and children this usually involves taking a blood sample from a vein. Some genetic tests can be done from samples of saliva or from taking a sample (swab) from the inside of your mouth.
In pregnancy, a sample may be taken from the baby by amniocentesis or chorionic villus sampling. In amniocentesis a sample of the liquid (amniotic fluid) that surrounds a baby is taken. It is done by putting a needle though the tummy (abdomen) into the womb (uterus). In chorionic villus testing a sample of part of the placenta is taken. This is either done by inserting a needle into the abdomen like in amniocentesis or by putting a thin tube into the neck of the womb (cervix). Both tests involve a very small risk that you may have a miscarriage as a result of having the test. If you are offered these tests, doctors will discuss the risks involved to help you to make a choice about whether to have the test or not.
In recent years the Harmony test has become available. This can be used during pregnancy and is done using a sample of the mother's blood, so there is no risk of miscarriage as there is with amniocentesis or chorionic villus sampling.
In newborns, routine screening for genetic disorder such as phenylketonuria happens as part of a baby's heel prick test when they around 5 days old.
After the sample has been taken it is sent to the laboratory for testing.
It may take anywhere from weeks to months for the results of all the tests to come back. This depends on the type of genetic test you've had. Your doctor should advise you how long the results will be.
A variety of genetic tests can be bought individually, many now over the Internet, which usually involve scaping the inside of your cheek to obtain some cells for testing. These are not recommended by doctors. Many test for genetic disorders for which there is no treatment, so they can heighten anxieties if you test positive for one of these disorders. They may also test for diseases that you may never actually develop in the future if you do not have other risk factors. For example, testing positive for the BRAC1 gene does not mean that you will definitely develop breast cancer in the future.
Before you undergo any of these tests, it may be worth asking yourself if you are prepared to make changes in your lifestyle, based on the test results. If you are not willing to take actions like stopping smoking or exercising more, such tests may not be of much benefit to you.
Many of these tests are also unreliable and can lead to very misleading results. If you would like to be tested for a genetic disorder then you should talk to your doctor about this in more detail.
The information obtained from genetic testing can have a profound impact on your life so you may be referred to a genetic counsellor Genetic counselling is available to anyone undergoing, or thinking of undergoing, any form of genetic testing. Genetic counselling is not a psychological therapy. It aims to provide you with all the information you need to make a decision about whether you should have a genetic test.
Genetic counselling may include information about:
The information is given in a way that will allow you to make your own decision. Only you can decide what is right for you. The counselling is essential to make sure you have all the important information you need to make the decision.
As they consider the options available to them, people are influenced by:
Post-test counselling is also available to help you deal with the results of the test.
More:
Genetic Testing: How It Works, Types, and Diagnosis | Patient
Genetic Testing Fact Sheet – NCI – National Cancer Institute
Genetic testing can give several possible results: positive, negative, true negative, uninformative negative, variant of uncertain significance, or benign (harmless) variant.
Positive result. A positive test result means that the laboratory found a genetic variant that is associated with an inherited cancer susceptibility syndrome. A positive result may:
Also, people who have a positive test result that indicates that they have an increased risk of developing cancer in the future may be able to take steps to lower their risk of developing cancer or to find cancer earlier, including:
Negative result. A negative test result means that the laboratory did not find the specific variant that the test was designed to detect. This result is most useful when a specific disease-causing variant is known to be present in a family. In such a case, a negative result can show that the tested family member has not inherited the variant that is present in their family and that this person therefore does not have the inherited cancer susceptibility syndrome tested for. Such a test result is called a true negative. A true negative result does not mean that there is no cancer risk, but rather that the risk is probably the same as the cancer risk in the general population.
When a person has a strong family history of cancer but the family has not been found to have a known variant associated with a hereditary cancer syndrome, a negative test result is classified as an uninformative negative (that is, it typically does not provide useful information).
In the case of a negative test result, it is important that the persons doctors and genetic counselors ensure that that person is receiving appropriate cancer screening based on that persons personal and family history and any other risk factors they may have. Even when the genetic testing is negative, some individuals may still benefit from increased cancer surveillance.
Variant of uncertain significance. If genetic testing shows a change that has not been previously associated with cancer, the persons test result may report a variant of uncertain significance, or VUS. This result may be interpreted as uncertain, which is to say that the information does not help to clarify their risk and is typically not considered in making health care decisions.
Some gene variants may be reclassified as researchers learn more about variants linked to cancer. Most often, variants that were initially classified as variants of uncertain significance are reclassified as being benign (not clinically important), but sometimes a VUS may eventually be found to be associated with increased risks for cancer. Therefore, it is important for the person who is tested to keep in touch with the provider who performed thegenetic testing to ensure that they receiveupdates if any new information on thevariant is learned.
Benign variant. If the test reveals a genetic change that is common in the general population among people without cancer, the change is called a benign variant. Everyone has commonly occurring benign variants that are not associated with any increased risk of disease.
Genetic test results are based on the best scientific information available at the time of the testing. While unfortunately no testing can be 100% error free, most genetic testing is quite accurate. However, it is very important to have thegenetic testing orderedby a provider knowledgeable in cancer genetics who can choose a reputable testing lab to ensure the most accurate test results possible.
Excerpt from:
Genetic Testing Fact Sheet - NCI - National Cancer Institute
Tempted to have genetic testing? First ask why – Harvard Health
When it comes to health and disease and, of course, many other aspects of life one thing is certain: genes matter. A single gene mutation can cause some conditions, such as sickle cell anemia and cystic fibrosis. More often, multiple genes are involved in disease development, and they act in concert with nongenetic factors, such as diet or exercise, to affect disease risk.
Several companies offer you the opportunity to look at your genes. But how might that help you from a health standpoint? And how do such tests differ from the genetic testing a doctor may recommend?
Consider the example of familial hypercholesterolemia (FH), a condition in which multiple variants of several different genes lead to markedly high cholesterol. This greatly increases the risk of heart attack, stroke, and other health problems. FH affects about one in 300 adults, which means it isnt rare. Among adults who have the most common genetic variants that cause it, heart attack or sudden cardiac death may occur in middle age. Children who have a double dose of a gene variant linked to this condition may die of cardiovascular disease before age 20. Earlier treatments intended to reduce the risk of complications, such as cholesterol-lowering drugs, are available if a child or adult is known to have a mutation linked to FH.
In recent years, theres been a dramatic increase in genetic testing. It was nearly unheard of only a few decades ago. Now, you or someone you know has likely had genetic testing within the last year or two.
And while healthcare providers can now order far more genetic tests for their patients than in the past, you dont need a doctors order to request this. 23andMe, Ancestry.com, and a number of other testing companies are ready and willing to check your genes for variants associated with certain health conditions, as well as your family ancestry. In fact, spending on direct-to-consumer genetic testing is predicted to reach $2.5 billion within the next few years.
For some people, the answer is clearly yes. When performed accurately, genetic tests can uncover a disease or a tendency to develop certain conditions, and it can lead to close relatives getting tested as well. Preventive measures or treatment can be lifesaving. Here are four examples (though there are many more).
In these cases, knowing you might develop a condition or are a carrier can help direct medical care, and may inform life decisions or encourage you or other family members to consider genetic counseling.
But the answer can also be no. Results of genetic testing may provide information you already know, may be unhelpful, or may even be misleading. For example, testing could reveal that you have a genetic mutation that rarely causes any health problems. Learning that you have this mutation may not help you though it might alarm you. Or, learning youre at increased risk for developing Alzheimers disease late in life may be more upsetting than useful, as there are currently no reliably effective preventive treatments.
Genetic testing may have more than one kind of cost. A genetic test ordered by your doctor for a specific medical reason may be covered by your health insurance, but its unlikely that an over-the-counter test will be. And, as one company states on its website, "knowing about genetic risks could affect your ability to get some kinds of insurance."
A 2021 study published in the medical journal JAMA Cardiology demonstrates how direct-to-consumer testing may be misleading.
The researchers looked at genetic testing for familial hypercholesteremia. They compared the results from a comprehensive panel of genetic testing ordered by doctors (which included more than 2,000 gene variants) with results from the more limited genetic testing (24 variants) provided by 23andMe.
Among more than 4,500 people tested for a medical reason, such as evaluating an unexpectedly high cholesterol level, the more limited testing would have missed important genetic variants for
This suggests that a large number of people would be falsely reassured by the results of their genetic tests for FH if they relied on the type of screening offered by a popular over-the-counter product. And results may be particularly unreliable among persons of color.
Its true that you cant pick your genes. But thanks to an ever-expanding menu of options, you can pick your tests. In many cases, its best to review your decision to have genetic testing with your doctor before having it done. You may choose to see a genetic counselor about the ramifications of testing before you jump in and let your doctor do the testing, rather than ordering it yourself. Or, you may decide the best plan is no testing at all.
Follow me on Twitter @RobShmerling
More:
Tempted to have genetic testing? First ask why - Harvard Health
DNA Test – Genetic Testing Overview – Cleveland Clinic
OverviewWhat is genetic testing?
Genetic testing may also be called DNA testing. Its a type of test that can identify changes in the genes, chromosomes or proteins in your body. Genetic testing takes a sample of your blood, skin, hair, tissue or amniotic fluid. The test may be able to confirm or rule out if you have a genetic condition. It may also help determine your chances of developing or passing on a genetic disorder.
Genetic testing looks for changes in your genes, chromosomes and proteins. DNA tests can give you lots of information about the genes that make up who you are. They can confirm if you have or dont have a specific disease. They can determine if you have a higher risk of developing certain conditions. And they can find out if you carry a specific mutated gene that you can pass to your child.
The various types of genetic tests include tests that look at:
Mutations in the genes or chromosomes in your developing baby (fetus) can be detected through a prenatal DNA test while youre pregnant. Prenatal testing doesnt test for all possible conditions. But it can determine the chances of your baby being born with certain conditions that we know how to look for. If your baby has an increased risk of having a genetic condition because of the familys genetic history, your healthcare provider may recommend prenatal testing.
Diagnostic testing can confirm or rule out specific genetic diseases or chromosomal problems. But it doesnt test for all genetic conditions. Diagnostic genetic testing is often used during pregnancy, but it can be used at any time to confirm a diagnosis if you have symptoms of a certain disease.
If a condition is autosome recessive, it means that someone can carry a gene for that condition but not have symptoms. Carrier testing can tell you if you carry a copy of a mutated gene for an autosomal recessive disease. This is generally done because one parents family has a history of a disease that is passed on in an autosomal recessive way, which means that it takes a copy of the gene from each parent. So if one parent knows they carry an autosomal recessive gene, the other should be tested so they know the risk of passing that disease to their kids.
Preimplantation testing can find genetic mutations in the embryos that were made using assisted reproductive techniques (ART), like in-vitro fertilization (IVF). A small number of cells are taken from your embryos and tested for certain mutations. Only embryos without these mutations are implanted in your uterus to attempt to start a pregnancy.
Your newborn will be tested two days after theyre born. A newborn screening tests for certain genetic, metabolic or hormone-related conditions. Newborns are screened immediately after birth so treatment can start right away if needed. States decide which diseases to screen for, but in the United States, hospitals can screen for more than 35 conditions in newborns.
Gene mutations that increase your likelihood of developing a genetic condition later in life can sometimes be detected through predictive and pre-symptomatic testing by looking for changes in your genes that increase your risk of developing certain diseases. These include certain types of cancer such as breast cancer. Presymptomatic testing can tell whether youll develop a genetic disorder before youve developed any symptoms, but not with 100% certainty. There is always a chance for errors when this type of testing is done, so speak with your provider about this before you do it.
Its important to remember that while genetic testing can detect some conditions, it doesnt detect everything. In addition, a positive result doesnt necessarily mean youll develop a condition. But genetic testing can be useful to confirm or rule out many different diseases and conditions. These conditions include:
Your healthcare provider will collect a sample of your blood, hair, skin, tissue or amniotic fluid. Amniotic fluid is the fluid that surrounds your developing baby (fetus) during your pregnancy. Your healthcare provider will send the sample to a laboratory. At the lab, technicians will look for changes in your genes, chromosomes or proteins. The technicians send the test results to your healthcare provider.
The physical risks of most genetic tests are small. Prenatal testing does carry a small risk of losing your pregnancy (miscarriage). This is because the test requires a sample of amniotic fluid from around your developing baby.
The greater risks of genetic testing are emotional and financial. If you receive unexpected results, you may feel angry, scared, depressed, anxious or guilty. In addition, genetic testing can cost anywhere from hundreds to thousands of dollars. Insurance may cover the cost of genetic testing. But it often depends on the type of test and the reason for the test.
Also, genetic testing doesnt provide information about all possible genetic conditions and not all of them are 100% accurate. And they dont necessarily tell you about how severe symptoms may be or when a certain genetic condition may develop.
The results of your DNA test are not always straightforward. Your healthcare provider will use the type of DNA test, your medical history and your family history to interpret the results. Then theyll go over the specific results with you. The results may be any of the following:
Two measures of accuracy apply to genetic tests. Analytical validity looks at whether a DNA test can accurately detect whether a specific gene has a mutation or not. Clinical validity means if there is a mutation, is it related to a specific disease or condition. All labs that perform DNA tests are regulated by federal and/or state standards. The standards are designed to ensure the accuracy of genetic tests.
Some test results may only take a few days. Prenatal test results are usually returned very quickly. Other tests take several weeks to get the results back. Your healthcare provider will give you specific information regarding the timing of your test results.
You should try to find a provider or genetic counselor near you to perform DNA testing. They will order the correct tests and then talk to you about what they mean. But if you cant go through your healthcare provider, you can get a DNA test kit directly from a DNA testing company. These test kits are called direct-to-consumer (DTC) genetic tests. The best DNA test kits offer easy-to-understand information about the scientific basis of their tests, but it is risky to use them because there may not be anyone you can speak to personally about the results.
If you test positive for a genetic condition or find that you have a higher risk of developing a disease, you should call your healthcare provider. They can put you in touch with a genetic counselor who can evaluate you and the information you have and help you decide what to do next.
Scientists discovered a technique called Restriction Fragment Length Polymorphism (RFLP) analysis in the 1980s. This analysis became the first genetic test to use DNA. But in the 1990s, Polymerase Chain Reaction (PCR) DNA testing was introduced. This type of DNA testing replaced RFLP testing. The science of DNA testing is constantly changing.
A DNA paternity test can determine whether a person assigned male at birth is another persons biological father. You can determine whether someone could be the biological father of your baby or child through a DNA cheek swab or blood test. Paternity tests can also be done using a prenatal paternity test during pregnancy.
A note from Cleveland Clinic
DNA tests (genetic testing) can help you determine if you have a genetic condition or if youre more likely to develop one. Genetic testing may give you peace of mind, but it also comes with many risks and limitations. If youre interested in taking a genetic test, call your healthcare provider. They can refer you to a genetic counselor to give you more information about the process.
See the article here:
DNA Test - Genetic Testing Overview - Cleveland Clinic
Genetic Disorders: What Are They, Types, Symptoms & Causes
OverviewWhat are genetic disorders?
Genetic disorders occur when a mutation (a harmful change to a gene, also known as a pathogenic variant) affects your genes or when you have the wrong amount of genetic material. Genes are made of DNA (deoxyribonucleic acid), which contain instructions for cell functioning and the characteristics that make you unique.
You receive half your genes from each biological parent and may inherit a gene mutation from one parent or both. Sometimes genes change due to issues within the DNA (mutations). This can raise your risk of having a genetic disorder. Some cause symptoms at birth, while others develop over time.
Genetic disorders can be:
There are many types. They include:
Chromosomal disorders
Multifactorial disorders
Monogenic disorders
Genetic disorders may also cause rare diseases. This group of conditions affects fewer than 200,000 people in the U.S. According to experts, there may be as many as 7,000 of these diseases.
Rare genetic disorders include:
To understand genetic disorder causes, its helpful to learn more about how your genes and DNA work. Most of the DNA in your genes instructs the body to make proteins. These proteins start complex cell interactions that help you stay healthy.
When a mutation occurs, it affects the genes protein-making instructions. There could be missing proteins. Or the ones you have do not function properly. Environmental factors (also called mutagens) that could lead to a genetic mutation include:
Symptoms vary depending on the type of disorder, organs affected and how severe it is. You may experience:
If you have a family history of a genetic disorder, you may wish to consider genetic counseling to see if genetic testing is appropriate for you. Lab tests can typically show whether you have gene mutations responsible for that condition. In many cases, carrying the mutation does not always mean youll end up with it. Genetic counselors can explain your risk and if there are steps you can take to protect your health.
If theres a family history, DNA testing for genetic disorders can be an important part of starting a family. Options include:
Most genetic disorders do not have a cure. Some have treatments that may slow disease progression or lessen their impact on your life. The type of treatment thats right for you depends on the type and severity of the disease. With others, we may not have treatment but we can provide medical surveillance to try to catch complications early.
You may need:
There is often little you can do to prevent a genetic disorder. But genetic counseling and testing can help you learn more about your risk. It can also let you know the likelihood of passing some disorders on to your children.
Some conditions, including certain rare and congenital diseases, have a grim prognosis. Children born with anencephaly typically survive only a few days. Other conditions, like an isolated cleft lip, do not affect lifespan. But you may need regular, specialized care to stay comfortable.
When you are living with a genetic disorder, you may have frequent medical needs. Its important to see a healthcare provider specializing in the condition. They are more likely to know which treatments are best for your needs.
You may also benefit from the support of others. Genetic disorders often have local or national support groups. These organizations can help you access resources that make life a little easier. They may also host events where you can meet other families going through similar challenges.
A note from Cleveland Clinic
Genetic disorders occur when a mutation affects your genes or chromosomes. Some disorders cause symptoms at birth, while others develop over time. Genetic testing can help you learn more about the likelihood of experiencing a genetic disorder. If you or a loved one have a genetic disorder, its important to seek care from an experienced specialist. You may be able to get additional information and help from support groups.
See the rest here:
Genetic Disorders: What Are They, Types, Symptoms & Causes
The Genetics of Cancer – NCI
On This Page
Is cancer a genetic disease?
Genetic changes that cause cancer can be inherited or arise from certain environmental exposures. Genetic changes can also happen because of errors that occur as cells divide.
Credit: National Cancer Institute
Yes, cancer is a genetic disease. It is caused by changes in genes that control the way cells grow and multiply. Cells are the building blocks of your body. Each cell has a copy of your genes, which act like an instruction manual.
Genes are sections of DNA that carry instructions to make a protein or several proteins. Scientists have found hundreds of DNA and genetic changes (also called variants, mutations, or alterations) that help cancer form, grow, and spread.
Cancer-related genetic changes can occur because:
DNA changes, whether caused by a random mistake or by a carcinogen, can happen throughout our lives and even in the womb. While most genetic changes arent harmful on their own, an accumulation of genetic changes over many years can turn healthy cells into cancerous cells. The vast majority of cancers occur by chance as a result of this process over time.
Is cancer hereditary?
Determining breast cancer risk: The discovery of BRCA1 and BRCA2 gene mutations improved screening and treatment decisions for breast and ovarian cancers.
Cancer itself cant be passed down from parents to children. And genetic changes in tumor cells cant be passed down. But a genetic change that increases the risk of cancer can be passed down (inherited) if it is present in a parent's egg or sperm cells.
For example, if a parent passes a mutated BRCA1 or BRCA2 gene to their child, the child will have a much higher risk of developing breast and several other cancers.
Thats why cancer sometimes appears to run in families. Up to 10% of all cancers may be caused by inherited genetic changes.
Inheriting a cancer-related genetic change doesnt mean you will definitely get cancer. It means that your risk of getting cancer is increased.
What is a family cancer syndrome?
A family cancer syndrome,also called ahereditary cancer syndrome, is a rare disorder in which family members have a higher-than-average risk of developing a certain type or types of cancer. Family cancer syndromes are caused by inherited genetic variants in certain cancer-related genes.
With some family cancer syndromes, people tend to develop cancer at an early age or have other noncancer health conditions.
For example, familial adenomatous polyposis (FAP) is a family cancer syndrome caused by certain inherited changes in the APC gene. People with FAP have a very high chance of developing colorectal cancer at an early age and are also at risk of developing other kinds of cancer.
But not all cancers that appear to run in families are caused by family cancer syndromes. A shared environment or habits, such as exposure to air pollution or tobacco use, may cause the same kind of cancer to develop among family members.
Also, multiple family members may develop common cancers, such as prostate cancer, just by chance. Cancer can also run in a family if family members have a combination of many genetic variants that each have a very small cancer risk.
Should I get genetic testing for cancer risk?
Certain genetic tests can show if youve inherited a genetic change that increases your risk of cancer. This testing is usually done with a small sample of blood, but it can sometimes be done with saliva, cells from inside the cheek, or skin cells.
Genetic tests can help families with a history of breast and ovarian cancer make screening and treatment decisions.
Not everyone needs to get genetic testing for cancer risk. Your doctor or health care provider can help you decide if you should get tested for genetic changes that increase cancer risk. They will likely ask if you have certain patterns in your personal or family medical history, such as cancer at an unusually young age or several relatives with the same kind of cancer.
If your doctor recommends genetic testing, talking with a genetic counselor can help you consider the potential risks, benefits, and drawbacks of genetic testing in your situation. After testing, a genetic counselor, doctor, or other health care professional trained in genetics can help you understand what the test results mean for you and for your family members.
Although its possible to order an at-home genetic test on your own, these tests have many drawbacks and are not generally recommended as a way to see whether you have inherited a genetic change that increases cancer risk.
For more information on what tests are available and who may want to consider them, see Genetic Testing for Inherited Cancer Susceptibility Syndromes.
How can I find out what genetic changes are in my cancer?
If you have cancer, a different type of genetic test called a biomarker test can identify genetic changes that may be driving the growth of your cancer. This information can help your doctors decide which therapy might work best for you or if you may be able to enroll in a particular clinical trial. For more information, see Biomarker Testing for Cancer Treatment. Biomarker testing may also be called tumor profiling or molecular profiling.
Biomarker testing is different from the genetic testing that is used to find out if you have an inherited genetic change that makes you more likely to get cancer. Biomarker testing is done using a sample of your cancer cellseither a small piece of a tumor or a sample of your blood.
In some cases, the results of a biomarker test might suggest that you have an inherited mutation that increases cancer risk. If that happens, you may need to get another genetic test to confirm whether you truly have an inherited mutation that increases cancer risk.
Who can see my genetic test results?
Your genetic counselor, doctors, and other health care professionals might see your genetic test results. In addition, your health insurance company has legitimate, legal access to your medical records.
Legal protections prevent discrimination on the basis of genetic test results, including the Genetic Information Nondiscrimination Act of 2008(GINA) and the Privacy Rule of the Health Information Portability and Accountability Act of 1996 (HIPAA).
How do genetic changes cause cancer?
Genetic changes can lead to cancer if they alter the way your cells grow and spread. Most cancer-causing DNA changes occur in genes, which are sections of DNA that carry the instructions to make proteins or specialized RNA such as microRNA.
For example, some DNA changes raise the levels of proteins that tell cells to keep growing. Other DNA changes lower the levels of proteins that tell cells when to stop growing. And some DNA changes stop proteins that tell cells to self-destruct when they are damaged.
For a healthy cell to turn cancerous, scientists think that more than one DNA change has to occur. People who have inherited a cancer-related genetic change need fewer additional changes to develop cancer. However, they may never develop these changes or get cancer.
As cancer cells divide, they acquire more DNA changes over time. Two cancer cells in the same tumor can have different DNA changes. In addition, every person with cancer has a unique combination of DNA changes in their cancer.
For more information on the biological changes that make cells cancerous, see What is Cancer? Differences between Cancer Cells and Normal Cells.
What kinds of genetic changes cause cancer?
Fusion proteins, which can occur when parts of different chromosomal regions are joined, may drive the development of many cancers in children.
Credit: Shannon McArdel, Ph.D. Harvard University SITN Blog, June 2017. CC BY-NC-SA 4.0.
Multiple kinds of genetic changes can lead to cancer. One genetic change, called a DNA mutation or genetic variant, is a change in the DNA code, like a typo in the sequence of DNA letters.
Some variants affect just one DNA letter, called a nucleotide. A nucleotide may be missing, or it may be replaced by another nucleotide. These are called point mutations.
For example, around 5% of people with cancer have a point mutation in the KRAS gene that replaces the DNA letter G with A. This single letter change creates an abnormal KRAS protein that constantly tells cells to grow.
Cancer-causing genetic changes can also occur when segments of DNAsometimes very large onesare rearranged, deleted, or copied. These are called chromosomal rearrangements.
For example, most chronic myelogenous leukemias (a type of blood cancer) are caused by a chromosomal rearrangement that places part of the BCR gene next to the ABL gene. This rearrangement creates an abnormal protein, called BCR-ABL, that makes leukemia cells grow out of control.
Some cancer-causing DNA changes occur outside genes, in sections of DNA that act like on or off switches for nearby genes. For example, some brain cancer cells have multiple copies of on switches next to genes that drive cell growth.
Other DNA changes, known as epigenetic changes, can also cause cancer. Unlike genetic variants, epigenetic changes (sometimes called epimutations) may be reversible and they dont affect the DNA code. Instead, epigenetic changes affect how DNA is packed into the nucleus. By changing how DNA is packaged, epigenetic changes can alter how much protein a gene makes.
Some substances and chemicals in the environment that cause genetic changes can also cause epigenetic changes, such as tobacco smoke, heavy metals like cadmium, and viruses like Epstein-Barr virus.
Read the original post:
The Genetics of Cancer - NCI
Understanding Genetic Testing for Cancer Risk
What is genetic testing?
Genetic testing is the use of medical tests to look for certain mutations (changes) in a persons genes. Many types of genetic tests are used today, and more are being developed.
Genetic testing can be used in many ways, but here well focus on how it is used to look for gene changes that are linked to cancer. (To learn about the role of genes and how mutations can lead to cancer, seeGenes and Cancer.)
Predictive genetic testing is a type of testing used to look for inherited gene mutations that might put a person at higher risk of getting certain kinds of cancer. This type of testing might be suggested for:
Most people (even people with cancer) do not need this type of genetic testing. Its usually done when family history suggests that a cancer may be inherited (see below) or if cancer is diagnosed at an uncommonly young age.
Genetic counseling and testing may be recommended for people who have hadcertain cancers or certain patterns of cancer in their family. If you have any of the following, you might consider talking to a genetic counselor about genetic testing:
If you are concerned about a pattern of cancer in your family, cancer youve had in the past, or other cancer risk factors, you may want to talk to a health care provider about whether genetic counseling and testing might be a good option for you.
You need to know your family history and what kinds of tests are available. For some types of cancer, no known mutations have been linked to an increased risk.
For more information on the types of cancer that may be linked to inherited genes,see Family Cancer Syndromes.
Genetic counseling gives you information that you and your family can use to make decisions about whether to get genetic testing (see below).
Genetic counselors have special training in the field of genetic counseling. Most are board-certified, and some might have a license depending on the rules in their state. Some doctors, advanced practice oncology nurses, social workers, and other health professionals may also provide genetic counseling, although they might have different levels of training in this field. If you are offered genetic counseling, its fair to ask about their training in this area.
Before and after genetic testing, genetic counseling can help you understand what your test results might mean, your risk of developing cancer, and what you can do about this risk. It is your decision to have testing and what steps you take after.
Its important to find out how useful genetic testing might be for you before you do it. Talk to your health care provider and plan on getting genetic counseling before the actual test. This will help you know what to expect. Yourcounselor can also tell you about the risks and benefits of the test, what the results might mean, and what your options are.
Your health care provider can refer you to a genetic counselor in your area, or you can find a list of certified genetic counselors on the website of the National Society of Genetic Counselors.
To learn more, see What Should I Know Before Getting Genetic Testing?
Sometimes after a person has been diagnosed with cancer, the doctor will order tests on a sample of cancer cells to look for certain gene or protein changes. These tests can sometimes give information on a persons outlook (prognosis), and they might also help tell if certain types of treatment may be useful.
These types of tests look for acquired gene changesonlyin the cancer cells. These tests are not the same as the tests used to find out about inherited cancer risk.
For more about this kind of testing and its use in cancer treatment, see Biomarker Tests and Cancer Treatment.
Some tests that look for gene changes can be bought without needing a doctors order. For this type of testing, you purchase a test kit and send a sample of your DNA (often from saliva) to a lab for testing.
If you are considering using a home-based genetic test (also known as a direct-to-consumer genetic test), you need to know what its testing for, what it can (and cant) tell you, and how reliable the test is.
Home-based tests do not provide information on a persons overall risk of developing any type of cancer. Sometimes these tests can sound much more helpful and certain than they have been proven to be. It may sound like the test will provide an answer to your specific health concern, such as your risk of hereditary cancer, but the test may not be able to answer that question completely. For example, a test may look for mutations in a certain gene, but it might not test for all of the possible mutations. So a negative test result, even if accurate, may miss the bigger picture regarding your cancer risk and what you can do to manage it. And you might not be provided with the important context about the test results that a genetic counselor could provide.
Home-based genetic tests should not be used instead ofcancer screeningorgenetic counselingthat may be recommended by a medical professional based on your individual risk for cancer.Always consult with your doctor if you are considering or have questions aboutgenetic testing. Trained genetic counselors can help you know whatto expect from your test results.
Prenatal Genetic Diagnostic Tests | ACOG
Amniocentesis: A procedure in which amniotic fluid and cells are taken from the uterus for testing. The procedure uses a needle to withdraw fluid and cells from the sac that holds the fetus.
Amniotic Fluid: Fluid in the sac that holds the fetus.
Aneuploidy: Having an abnormal number of chromosomes.
Cells: The smallest units of a structure in the body. Cells are the building blocks for all parts of the body.
Chorionic Villus Sampling (CVS): A procedure in which a small sample of cells is taken from the placenta and tested.
Chromosomes: Structures that are located inside each cell in the body. They contain the genes that determine a person's physical makeup.
Cystic Fibrosis: An inherited disorder that causes problems with breathing and digestion.
Diagnostic Tests: Tests that look for a disease or cause of a disease.
DNA: The genetic material that is passed down from parent to child. DNA is packaged in structures called chromosomes.
Embryo: The stage of development that starts at fertilization (joining of an egg and sperm) and lasts up to 8 weeks.
Fetus: The stage of human development beyond 8 completed weeks after fertilization.
Fluorescence In Situ Hybridization (FISH): A screening test for common chromosome problems. The test is done using a tissue sample from an amniocentesis or chorionic villus test.
Genes: Segments of DNA that contain instructions for the development of a person's physical traits and control of the processes in the body. The gene is the basic unit of heredity and can be passed from parent to child.
Genetic Counselor: A health care professional with special training in genetics who can provide expert advice about genetic disorders and prenatal testing.
Genetic Disorders: Disorders caused by a change in genes or chromosomes.
Hospice Care: Care that focuses on comfort for people who have an illness that will lead to death.
In Vitro Fertilization (IVF): A procedure in which an egg is removed from a woman's ovary, fertilized in a laboratory with the man's sperm, and then transferred to the woman's uterus to achieve a pregnancy.
Karyotype: An image of a person's chromosomes, arranged in order of size.
Microarray: A technology that examines all of a person's genes to look for certain genetic disorders or abnormalities. Microarray technology can find very small genetic changes that can be missed by the routine genetic tests.
Monosomy: A condition in which there is a missing chromosome.
Mutations: Changes in a gene that can be passed on from parent to child.
ObstetricianGynecologist (Ob-Gyn): A doctor with special training and education in women's health.
Placenta: An organ that provides nutrients to and takes waste away from the fetus.
Preimplantation Genetic Diagnosis: A type of genetic testing that can be done during in vitro fertilization. Tests are done on the fertilized egg before it is transferred to the uterus.
Screening Tests: Tests that look for possible signs of disease in people who do not have signs or symptoms.
Sickle Cell Disease: An inherited disorder in which red blood cells have a crescent shape, which causes chronic anemia and episodes of pain.
TaySachs Disease: An inherited disorder that causes intellectual disability, blindness, seizures, and death, usually by age 5.
Trisomy: A condition in which there is an extra chromosome.
Ultrasound Exam: A test in which sound waves are used to examine inner parts of the body. During pregnancy, ultrasound can be used to check the fetus.
Uterus: A muscular organ in the female pelvis. During pregnancy, this organ holds and nourishes the fetus. Also called the womb.
See the original post here:
Prenatal Genetic Diagnostic Tests | ACOG
DiGeorge Syndrome – StatPearls – NCBI Bookshelf
Continuing Education Activity
DiGeorge syndrome (DGS) is a congenital disorder with a broad phenotypic presentation, which results predominantly from the microdeletion of chromosome 22 at a location known as 22q11.2. This mutation results in the failure of appropriate development of the pharyngeal pouches, which are responsible for the embryologic development of the middle and external ear, maxilla, mandible, palatine tonsils, thyroid, parathyroids, thymus, aortic arch, and cardiac outflow tract. Features of DGS include cardiac anomalies, recurrent infections, abnormal facies, thymic hypoplasia or aplasia, cleft palate, developmental delay, and hypocalcemia. This activity outlines the diagnosis, evaluation, treatment, and management of patients with DGS, and highlights the role of the interprofessional team in managing patients with this condition.
Objectives:
Summarize the etiology of DiGeorge syndrome and its broad phenotypic presentation.
Review the evaluation of patients with DiGeorge syndrome.
Explain the treatment and management options available for DiGeorge syndrome.
Outline interprofessional team strategies for improving care coordination and communication to advance the care of patients with DiGeorge syndrome and improve outcomes.
DiGeorge Syndrome (DGS) is a combination of signs and symptoms caused bydefects in the development of structures derived from the pharyngeal archesduring embryogenesis. Features of DGSwere first described in 1828 but properly reported by Dr. Angelo DiGeorge in 1965, as a clinical trialthat included immunodeficiency, hypoparathyroidism, and congenital heart disease.[1]
DGS is one of several syndromes that has historically grouped under a bigger umbrella called 22q11 deletion syndromes, which include Shprintzen-Goldberg syndrome, velocardiofacial syndrome, Cayler cardiofacial syndrome, Sedlackova syndrome, conotruncal anomaly face syndrome, and DGS.Although the genetic etiology of these syndromes may be the same, varying phenotypeshas supported the use of different nomenclature in the past, which has led to confusion in diagnosing patients with DGS, which causes potentially catastrophic delays in diagnosis.[2] Current literature supports the use of the names of these syndromes interchangeably.
Features ofDGSincludean absent or hypoplastic thymus, cardiac abnormalities, hypocalcemia, and parathyroid hypoplasia (See "History and Physical" below). Perhaps, the most concerning characteristic of DGS is the lack of thymic tissue, becausethisis the organ responsible for T lymphocyte development.A complete absence of the thymus, though very rare and affecting less than 1% of patients with DGS, is associated with a form of severe combined immunodeficiency (SCID).T-cells are a differentiated type of white blood cellspecializingin certain immune functions: destroying cells that are infected or malignant,existing as an integralpart of the innate immune system by killing viruses (e.g., Killer T-cells), helping B-cells matureto produce immunoglobulins for strongeradaptive immunity (e.g. helper T-cells), etc. The degree of immunodeficiency of patients with DGS can present differently depending onthe extent of thymic hypoplasia.
Somepatients may have a mild to moderate immune deficiency, and the majority of patients have cardiac anomalies.Other features include palatal, renal, ocular, and gastrointestinal anomalies. Skeletal defects, psychiatric disease, and developmental delay are also of concern. There are different opinions about syndrome-related alterations in cognitive development, and a cognitive decline rather than an early onset intellectual disability is observable.[3] The particularities of the clinical presentation requires observation on an individual basis, with careful evaluation and interprofessional treatment throughout the patient's life.
About 90% of DGS cases are a result of a deletion in chromosome 22, more specifically on the long arm (q) at the 11.2 locus (22q11.2). Most of these mutations arise de novo with no genetic abnormalities noted in the genome of the parents of children with DGS.[1] Researchers have identified over 90 different genes at this locus, some of which they have studied in mouse models.The most studied of these genes isT-box transcription factor 1 (TBX1), which correlates with severe defects in the development of the heart, thymus, and parathyroid glands of mouse models. TBX1 also correlates with neuromicrovascular anomalies, which may be responsible for the behavioral and developmental abnormalities seen in DGS.[4][5]
Microdeletion of 22q11.2 is the most common microdeletion syndrome, affecting approximately 0.1% of fetuses.[6]The rate of 22q11.2 microdeletion in live births occurs at an estimated rate of 1 in 4000 to 6000.[1][7] There are several explanations for the variance in fetal versus live birth prevalence. Firstly, current evidence may not comprise a large enough population. Secondly, 22q11.2 microdeletions may produceembryonically lethal phenotypes, which was observable in animal studies.
The prevalence of 22q11.2 microdeletion may be more common than supported in literature due to several factors. Firstly, not every patient with this microdeletion presents with several craniofacial abnormalities and hence does notundergo genetic testing. African-American children, for example, may not have the craniofacial abnormalities characteristic of DGS in other races. Secondly, access to healthcare, specifically genetic testing, is not available to every individual that might have the microdeletion, regardless of the severity of craniofacial dysmorphism. Further population studies are therefore needed to fully understand the extent and spectrum of 22q11.2 microdeletions in different populations.[8]
DGS results from microdeletion of 22q11.2, which encodes over 90 genes. Patients with DGS display a broad array of phenotypes, and the most common findings include cardiac anomalies, hypocalcemia, and hypoplastic thymus.
On a genetic basis, TBX1 has correlations with the most prominent phenotypes characteristic of DGS. Failure in embryologic developmentof the pharyngeal pouches, which is driven by TBX1, leads to absence or hypoplasia of the thymus and parathyroid glands.Mouse and zebrafishTBX1 knockout models have been studied to understand the embryologic basis of this disease. In mice, for instance, the absence of TBX1 causes severe pharyngeal, cardiac, thymic, and parathyroid defects as well as a behavioral disturbance.[9]Moreover, zebrafish knockouts have demonstrated defects in the thymus and pharyngeal arches as well as malformation of the ears and thymus.[10]
A 22q11.2 knockout mouse model has also been studied, with findings pertinent for molecular and behavioral changes seen in Parkinson's disease, autism spectrum disorder, attention deficit hyperactivity disorder, and schizophrenia.[11][12]These findings, as well as the neuromicrovascular pathology found in TBX1 knockout mice, suggest a molecular basis for the psychiatric pathologies associated with DGS.[4][5]Of note, individuals affected bythissyndrome have a 30-fold increased risk of developing schizophrenia.
A detailed history and physical is vital in the diagnosis and assessment of DiGeorge syndrome. A broad spectrum of disease severity exists, and suspicion of DGS from history and physical can prompt further evaluation. Although most cases get diagnosed in theprenatal and pediatric periods, diagnosis can also occur in adulthood.Delay in motor development is a common presenting feature first recognized by parentswho notice delays in rolling over, sitting up, or other infant milestones.[13]These findings can be associated with delayed speech developmentand learning disabilities. Later in life, abnormal behavior in the setting of poor developmental history may be thechief presenting symptom of DGS.[1]
A detailed history mayrevealthefollowing:
Family history of diagnosed or suspected DGS
Abnormalgenetic testing results of family members
Delays in the achievement of developmental milestones
Behavioral disturbance
Cyanosis, exercise intolerance, or symptoms
Recurrent infections secondary to T-cell deficiency
Speech difficulty
Difficulty feeding and/or failure to thrive
Muscle spasms, twitching, tetany, seizure
An examination can reveal findings consistent with severalfeatures of DGS:
A complete cardiopulmonary evaluation can reveal murmurs, cyanosis, clubbing, or edema consistent withaortic arch anomalies, conotruncal defects (e.g., tetralogy of Fallot, truncus arteriosus, pulmonary atresia with ventricular septal defect, transposition of the great vessels, interrupted aortic arch), or tricuspid atresia.
A craniofacial examination may demonstrate abnormalities such as cleft palate, hypertelorism, ear anomalies, short down slanting palpebral fissures, short philtrum, and hypoplasia of the maxilla or mandible.
Recurrent sinopulmonary infections due to T cell deficiency as a result of thymic hypoplasia
Signs of hypocalcemia, including twitching and muscle spasm, may be evident as a result of parathyroid hypoplasia. Chvostek's and Trousseau's signs may be positive.
Delayed development, unusual behavior, or signs of psychiatric disorders may be observable.
A clinician makes a definitive diagnosis of DGS in individuals with amicrodeletion of chromosome 22 at the 22q11.2 locus. Classic evaluations of genetic abnormalities, such as trisomies, including the Giemsa banding technique, are incapable of revealing microdeletions. Microdeletions responsible for DGS are therefore detected by fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA),single nucleotide polymorphism (SNP) array, comparative genomic hybridization (CGH) microarray, or quantitative polymerase chain reaction (qPCR). The availability and cost of these techniques can delay diagnosis, particularly in resource-poor settings.
Patients diagnosed with or suspected of having DGS should undergo extensive evaluation, particularly if life-threatening cardiac or immunologic deficits are present. The following testsshould merit consideration:
Echocardiogram to evaluateconotruncal abnormalities
Complete blood count with differential
T and B Lymphocyte subset panels
Flow cytometry to assess T cell repertoire
Immunoglobulin levels
Vaccine titers for evaluation of response to vaccines
Serum ionized calcium and phosphorus levels
Parathyroid hormone level
Chest x-ray for thymic shadow evaluation
Renal ultrasound for possible renal and genitourinary defects
Serum creatinine
TSH
Testing for growth hormone deficiency
It is important to note that the broad spectrum of disease severity makesthe evaluationofDGS particularlychallenging. Cases involving significant cardiac, thymic, and craniofacial deficits are more easily recognizable than those lacking severe features. Implementation of advancing genomic studies and facial recognition technology in modern medicinemay assist in more effective diagnosis and evaluation of DGS patients.[14]
Treatment and management of DGS require intensive interprofessional care:
Fortunately, many patients with DGS have minor immunodeficiency, with preservation of T cell function despite decreased T cell production. Frequent follow-up with an immunologist experienced in treating primary immunodeficiencies is advisable. Immunodeficiency in neonates with complete DGS (cDGS) requires management with isolation, intravenous IgG,antibioticprophylaxis, and either thymic or hematopoietic cell transplant (HSCT).
Cardiac anomalies, if not diagnosed during the fetal ultrasound, may present shortly after birth as life-threatening cyanotic heart disease. Pediatric cardiothoracic surgery evaluation may be urgently required. Blood products, if necessary, should be irradiated, CMV negative, and leukocyte reduced to prevent transfusion-associated graft-versus-host disease. These measures also aim to reduce lung injury, particularly in surgical cases requiring cardiopulmonary bypass.
Cleft palate cases require evaluation by an otolaryngologist, plastic surgeon, or oral & maxillofacial surgeon with experience in surgical correction of palatal defects. Repair ofa cleft palate can improve feeding ability, speech, and reduce the incidence of sinopulmonary infections.
Hypocalcemia is manageable with calcium and vitamin D supplementation. Recombinant human PTH is an option in DGS patients refractory to standard therapy.
Autoimmune diseases are common in DGS patients, includingimmune thrombocytopenia(ITP), rheumatoid arthritis, autoimmune hemolytic anemia, Graves disease, and Hashimoto thyroiditis. DGS patientsshould be evaluated carefully for autoimmune symptoms regularly.
Audiologic evaluationis necessary for DGS patients experiencing difficulty with hearing. Children too young to express difficulty with hearing need assessment, particularly with a delay in cognitive and behavioral development.
Early intervention services arebeneficial for children with impaired cognitive and behavioral development.
Speech therapy isnecessary for difficulty with language secondary to craniofacial anomalies and/or cognitive impairment.
Genetic counseling is a reasonable consideration for parents of a child with DGS who desire more children, as well as for patients with DGS who may want to become parents. If a parent has the same mutation as an affected child, there is a 50% chance a new baby will also have DGS.
Advanced approaches for the management of children withcomplete DiGeorge anomaly
In the cDGS featuring no thymus function andbone marrow stem cells can not develop into T cells, childrenusually die by age 2 years due to severe infections. In this setting, the proposal is to T cellreplete HSCT. Nevertheless, because of the absence of thymus, thisstrategy can only obtain engraftment of post thymic T cells.[17]A multicenter survey on the outcome of HSCT showed a survival rate of 33% after matched unrelated donors and 60% in the case of matched sibling transplantations.[18] Recently, the FDA approved the thymus transplantation as standard care. This approach focuses on producingnaive T cellswith a broad T-cell receptor set. The procedure takes place using general anesthesia, and thymus tissue usually gets transplanted into the recipient subject's quadriceps. Studies indicateup to 75% of long-term survival but have described frequent autoimmune sequelae (e.g., autoimmune hemolysis, thyroiditis, thrombocytopenia, enteropathy, and neutropenia) in survivors.[19]
All patient findings that are part ofDiGeorge syndrome can also be present as isolatedanomalies in an otherwise normal individual.
The following conditions present with overlapping features:
Smith-Lemli-Opitz syndrome - (polydactyly and cleft palate are common findings).
Oculo-auriculo vertebral (Goldenhar) syndrome (OAVS) - (ear anomalies, heart disease, vertebral defects,and renalanomalies are present). OAVS often demonstrates a sporadic presentation.
Alagille syndrome - (butterfly vertebrae,congenital heart disease, and posterior embryotoxon arecommon to both conditions).
VATER association (heart disease, vertebral, renal, and limb anomalies present in both conditions). VATER association is a diagnosis of exclusion for which an established etiology to date remains unknown.
CHARGE syndrome - (any combination ofcongenital heart disease, palatal differences, atresia choanae, coloboma, renal, growth deficiency, ear anomalies/hearing loss, facial palsy, developmental differences,genitourinary anomalies, and immunodeficiency are present in both syndromes).
Genetic consult is essential along with the complete clinical picture to make an accurate diagnosis of DiGeorge syndrome.
Less than 1% of patients with 22q11.2 microdeletion have complete DGS, the most severe subtype of DGS with a very poor prognosis. Without thymic or hematopoietic cell transplantation, these patients die by 12 months of age. Even with a transplant, however, prognosis remains poor. In a study of 50 infants who received a thymic transplant for complete DGS, only 36 survived to two years.[20]
Patients with partial DGS do not have a defined prognosis, as this depends on the severity of the pathologies associated with the disease. While some do not survive infancy due to severe cardiac anomalies, many survive into adulthood. DGS may be vastly underdiagnosed, and many undiagnosed adults with DGS thrive in the community with undetectable congenital anomalies and minor intellectual and/or social impairment. Improvements in genetic diagnostics will hopefully improve understanding of DGS in the future.
Cardiac and craniofacial anomalies associated with DGS may require surgical repair. As with any surgical procedure, the possibility of complications, including bleeding, infection, and prolonged hospitalization, exists. These risks are particularly dangerous for DGS patients with significant immunocompromise.
Consistent follow-up of patients with DGS is necessary to evaluate for possiblecomplications: severe recurrent infections, autoimmune diseases, and hematologic malignancies.
Parents of children with DGS should receive patient education as it pertains to the severity of their child's condition. Discussion topics may include the following:
Early signs and symptoms of infection
Signs of hypocalcemia
Safe use of medications
Surgical intervention options
Immune therapy options
Genetic counseling
Speech therapy for feeding or language difficulty
Developmental milestones and warning signs of developmental delay
Benefits of early intervention programs
Signs and symptoms of psychiatric disorders
DiGeorge syndrome is easy to remember using the "CATCH-22" mnemonic:
Conotruncal cardiac anomalies
Abnormal facies
Thymic hypoplasia
Cleft palate
Hypocalcemia
22q11.2 microdeletion
Management of DGS requires an interprofessional approach by a team of healthcare professionals. Obstetricians and genetic counselors can assist in diagnosis and management prenatally. Neonatologists, primary care pediatricians, family medicine physicians, immunologists, cardiothoracic surgeons, pediatricians, craniofacial surgeons, and othermedical specialties may be involved in the care of patients with DGS. Collaboration with nurses, pharmacists, psychologists, speech therapists, and other healthcare professionals is paramount. Pharmacists can verify agent selection and dosing with medications to address the endocrine aspects of the disease. Nursing can counsel parents and monitor treatment progress. Psychological professionals can assist with developmental difficulties, as well as work with family members. Patients with DGS require lifelong, consistent follow-up. Because numerous organs are involved, close follow up with each specialist is necessary. Open communication and collaboration between all members of the interprofessional healthcare team are vital to ensure good outcomes. [Level 5]
Diagnosis and management can be challenging, and the interprofessional team can provide a collaborative effort to reduce morbidity and mortality associated with DGS. Current evidence regarding the management of DGS reflects level 5 evidence, and treatment options require a tailored approach around the individual patient's disease manifestations.
DiGeorge syndrome. Contributed by Professor Victor Grech (CC By=S.A. 3.0 https://creativecommons.org/licenses/by-sa/3.0/) Image courtesy: https://en.wikipedia.org/wiki/DiGeorge_syndrome#/media/File:DiGeorge_syndrome1.jpg
DiGeorge syndrome karyotype. Image courtesy O Chaigasame
Go here to see the original:
DiGeorge Syndrome - StatPearls - NCBI Bookshelf
Genome Medical and Pierian Announce Collaboration to Optimize Genomic Testing Programs – Business Wire
SOUTH SAN FRANCISCO, Calif. & ST. LOUIS--(BUSINESS WIRE)--Genome Medical, the leading telehealth provider of genetic services and genomics-based care, and Pierian, the global leader in advanced clinical genomics technology and services, announced a collaboration designed to streamline and optimize onsite genomics programs for health care organizations and provider groups. The companies services, when combined with genomic testing capabilities, create an end-to-end patient and clinician experience that elevates standards of care and patient outcomes.
Genome Medical and Pierian are working together to efficiently identify patients who may benefit from genomic testing and an enhanced clinical genomics workflow. The combined solution for clinicians facilitates the ordering of appropriate testing which is then processed in onsite laboratories supported by Pierian.
First, through its RISE Patient Engagement Modules, Genome Medical helps clinicians Reach, Inform, Support and Educate patients. RISE includes a Hereditary Cancer Risk Assessment Module that collects and analyzes family and personal health history to determine if a patient meets genetic testing criteria for hereditary cancer. When criteria is met and testing is ordered, laboratory customers utilize Pierians advanced technology platform to ingest, analyze, interpret and report on genomic insights for more precise care.
For physician-owned or -managed service organizations, Pierian and Genome Medical deliver a streamlined path to in-house, high-quality precision medicine programs that provide recommended and appropriate care to all patients who meet national standards for genomic testing. This can also include virtual post-test genetic counseling from Genome Medicals nationwide team to help explain the test findings and advise on recommended follow-on care, if needed.
We are excited to partner with a like minded innovator, Genome Medical, to combine our leading edge platforms and expertise to enable the clinicians we are privileged to serve, said Mark McDonough, CEO of Pierian. At Pierian, we are passionately committed to catalyzing precision medicine at scale through our tools, our team, our customers, and our partners like Genome Medical. We are united in our belief that all patients deserve access to high quality, affordable, genetic testing.
Genome Medical has pioneered a virtual model of tech-enabled care delivery and assembled an unmatched team of genetic specialists, enabling rapid, efficient access to genetic counseling and related services. The company offers flexible genetic services programs to approximately 100 partners, including health systems, diagnostic testing labs, insurers, and other partners. In addition, its services are a covered, in-network benefit for more than 160 million people in the U.S.
Genome Medical is pleased to be able to partner with Pierian to bring our patient screening and clinical genetic services to provider groups who are looking to improve and expand their genomic testing programs, said Jill Davies, CEO of Genome Medical. This collaboration represents two industry leaders delivering the services and tools that will make in-house genomic testing programs accessible to a wider array of providers and patients.
Pierian partners with academic centers, health systems, physician-owned laboratories and reference laboratories worldwide to establish high-quality clinical genomics programs and a global sharing network. With advanced interpretation technology connected to the most comprehensive knowledge base, Pierians unique, adaptive learning algorithms make intelligent associations between comprehensive datasets and individual patient results. Post analysis and interpretation, clinical reports are easy to generate, which empowers clinicians with genomic insights to fulfill the promise of precision care.
About Genome Medical
Genome Medical, the leading genomic care delivery company, is personalizing health care for all through on-demand access to genetic insights and genomic medicine. We operate as an independent virtual medical practice, powered by a digital health technology platform. By partnering with health systems, providers, health plans, employers, labs and biopharmaceutical companies, we expand the reach and impact of precision medicine. We provide clinical assessments and tools, test recommendations and ordering, and personalized care plans to deliver optimal patient care and improve health outcomes. The company, which is headquartered in South San Francisco, has been honored as The Best Digital Health Company to Work For by Rock Health, Fenwick & West and Goldman Sachs in their Top 50 in Digital Health awards. To learn more, visit genomemedical.com and follow @GenomeMed.
About Pierian
Pierian is a partner in precision medicine, enabling clinicians and medical facilities to advance clinical genomics programs and modernize patient care. We believe in the potential of genomics to transform human health and are working to ensure that communities anywhere can experience the benefits. We curate the worlds genetic knowledge, and our advanced interpretation technology combines this knowledgebase with adaptive learning algorithms that connect diverse sources of information through machine learning. When applied in clinical settings our platform is paired with our enabling services which support workflow design, implementation, validation, interpretation, and reimbursement. For more information, visit http://www.pieriandx.com.
Originally posted here:
Genome Medical and Pierian Announce Collaboration to Optimize Genomic Testing Programs - Business Wire